Expression of sex hormone-binding globulin exon VII splicing variant mRNA in human uterine myometrium and leiomyoma.
We have explored the mechanism of estrogen-induced growth in human uterine leiomyomas from the aspect of sex hormone-binding globulin (SHBG) exon VII splicing variant mRNA expression using the reverse transcription-polymerase chain reaction-Southern blot and DNA sequencing analyses. The results were obtained by analysis of the missing base pairs corresponding to the entire exon VII, which are considered to encode a portion of the steroid-binding site. This absence replaces 118 amino acids from the carboxy-terminus of SHBG with nine different amino acid residues due to the formation of a new stop codon at residue 334. The ratio of the SHBG variant to its wild-type mRNA levels in uterine leiomyomas was reduced, compared with that in the corresponding myometria in individual cases, while the SHBG wild-type and variant mRNA levels showed no significant difference during the menstrual phase. These studies demonstrate coexpression of SHBG exon VII splicing variant mRNA with its wild-type in human uterine myometria and leiomyomas. The reduced expression of the SHBG variant to wild-type mRNA levels in leiomyoma might be involved in the intracellular estrogen-predominant milieu, plausibly assisting in the development and growth of the leiomyoma.
Misao
R
R
Department of Obstetrics and Gynecology, Gifu University School of Medicine, Japan.
Nakanishi
Y
Y
Fujimoto
J
J
Tamaya
T
T
D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D015139:Blotting, Southern; D004247:DNA; D004273:DNA, Neoplasm; D005091:Exons; D005260:Female; D006801:Humans; D007889:Leiomyoma / Q000378:metabolism*; D008875:Middle Aged; D008969:Molecular Sequence Data; D009215:Myometrium / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D012326:RNA Splicing; D016415:Sequence Alignment; D012738:Sex Hormone-Binding Globulin / Q000235:genetics*; D014594:Uterine Neoplasms / Q000235:genetics*
D004273:DNA, Neoplasm; D012738:Sex Hormone-Binding Globulin; D004247:DNA